小柯机器人

美国贝勒医学院Mauro Costa-Mattioli小组的研究揭示了宿主遗传学和微生物组在复杂行为中的贡献。2021年3月10日出版的《细胞》杂志发表了这项成果。

研究人员发现在神经发育障碍Cntnap2^-/-模型中，微生物组和宿主基因相互依赖地调节了许多适应不良行为。Cntnap2^-/-小鼠的过度活跃表型是由宿主遗传学造成的，而社交行为表型则是由肠道微生物组调控。有趣的是，扰乱特定微生物通过介导四氢蝶呤合成途径中代谢物的上调选择性地改善了Cntnap2^-/-小鼠的社交缺陷。

该发现表明行为异常可能由不同的成因（宿主遗传与微生物），这可能会改变人们对神经系统疾病的理解及其治疗方法。

据了解，一般认为许多神经系统疾病的核心症状是由影响大脑发育和功能的遗传变异造成。但是，肠道微生物组是另一个重要的变异来源，其也可以影响特定行为。因此，阐明宿主遗传变异、微生物组及其对复杂行为的作用至关重要。

附：英文原文

Title: Dissecting the contribution of host genetics and the microbiome in complex behaviors

Author: Shelly A. Buffington, Sean W. Dooling, Martina Sgritta, Cecilia Noecker, Oscar D. Murillo, Daniela F. Felice, Peter J. Turnbaugh, Mauro Costa-Mattioli

Issue&Volume: 2021-03-10

Abstract: The core symptoms of many neurological disorders have traditionally been thought tobe caused by genetic variants affecting brain development and function. However, thegut microbiome, another important source of variation, can also influence specificbehaviors. Thus, it is critical to unravel the contributions of host genetic variation,the microbiome, and their interactions to complex behaviors. Unexpectedly, we discoveredthat different maladaptive behaviors are interdependently regulated by the microbiomeand host genes in the Cntnap2/ model for neurodevelopmental disorders. The hyperactivity phenotype of Cntnap2/ mice is caused by host genetics, whereas the social-behavior phenotype is mediatedby the gut microbiome. Interestingly, specific microbial intervention selectivelyrescued the social deficits in Cntnap2/ mice through upregulation of metabolites in the tetrahydrobiopterin synthesis pathway.Our findings that behavioral abnormalities could have distinct origins (host geneticversus microbial) may change the way we think about neurological disorders and howto treat them.

DOI: 10.1016/j.cell.2021.02.009

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00159-8